动物模型,肝衰竭 z-bo 2020-08-07 533

　　(1) Model method Adult animals are anesthetized and fixed. The abdomen is opened along the midline of the abdomen, and a purse-string suture is made on the inferior vena cava above the renal vein with a 5-0 vascular suture. After finding the portal vein from the root of the small mesentery, it is freed from the hepatic portal to the level of the splenic vein, and the portal vein collateral branches are ligated and cut. Heparin was injected intravenously with 100 U/kg body weight. Clamp the portal vein at the level of the splenic vein, then clamp, cut and ligate under the fork of the portal part of the portal vein. Insert a shunt tube with anticoagulant down into the portal vein to the level of the splenic vein and ligate and fix it, insert the inferior vena cava through the purse-string upwards, and tighten the purse-string suture. Before inserting the inferior vena cava, a non-invasive vascular clamp was used to block the blood flow of the inferior vena cava at the upper and lower sides of the purse-string suture. The common bile duct is freed from the hepatoduodenal ligament, and then the hepatoduodenal ligament is double-ligated close to the duodenum to block all the hepatic arteries. Or after laparotomy, free the portal vein and inferior vena cava, perform end-to-side anastomosis or side-to-side anastomosis of the portal vein and inferior vena cava, and then close the hepatic artery on this basis. Rats can directly clamp the hepatic artery temporarily with a vascular clip, and experimental dogs or pigs can undergo a second operation 24 hours after the portal vena cava anastomosis to temporarily clamp the hepatic artery for 4-6 hours. Throughout the process of model making and experimentation, the animal’s blood pressure, pulse, and consciousness were continuously observed, and the time of death was recorded. At the same time, blood was drawn dynamically to prepare serum for liver function testing, and liver tissues were taken for morphological examination.

　　(2) Features of the model 30-60 minutes after the blood flow into the liver is completely blocked, the animals begin to restlessly and gradually enter a state of hepatic coma, the systolic blood pressure gradually decreases with time, and all of them die within 75-155h. The liver of dead animals was dark red, dull, and scattered with purple patches. Since the blood supply to the liver was blocked, the animal serum ALT, AST, LDH, and NH3 gradually increased, PT gradually increased, while fibrinogen (FIB) and GLU gradually decreased. The microscope showed that 2 hours after the hepatic blood flow was blocked, the Disch space was significantly expanded, the central vein collapsed, the intracytoplasmic vacuolar degeneration of the liver, the pyknosis of the nucleus, the disappearance of nucleoli, and the homogenization of glycogen particles in the cytoplasm Facial endoplasmic reticulum degranulates, mitochondrial edema, partial dissolution, nuclear chromatin accumulation, nuclear deformation, formation of pseudo-inclusion bodies in the nucleus; unrecognizable liver lobule structure in animals with liver failure, disordered liver cell arrangement, liver plate dissociation, and focal appearance And spot flaky liver cell necrosis.

　　(3) Comparative Medicine The acute liver ischemia model is currently an ideal animal model for inducing acute liver failure. Its surgical procedures include portal vena cava anastomosis and donor hepatic artery ligation. Among them, the donor hepatic artery ligation includes two methods: thorough ligation and temporary clamping. The former refers to the complete clamp or ligation and occlusion of the portal vein and hepatic artery, which is a complete blood supply block model. This model animal generally has a short time of death, has characteristics similar to the liver removal model, and is irreversible, so it is only suitable for short-term evaluation of in vitro bioartificial liver support systems, or for the study of intracranial pressure and cerebral edema related to acute liver failure The change. In the latter, after the portal vena cava anastomosis, the hepatic blood vessels are temporarily clamped by clamp or suspension wire pulling. After the acute liver ischemia leads to liver failure, the liver is released and the blood supply to the liver is restored. Ischemic model. Since the interval between anastomosis and hepatic artery ligation determines the number of collateral circulations, the latter has a significant correlation with the degree of acute liver failure and the time of death. Therefore, anastomosis and hepatic artery ligation The time interval is the key to the preparation of the model. Because this model is potentially reversible, it is suitable for longer-term bioartificial liver support experiments and observations. At present, most bioartificial liver animal experiments use this method, which is the most ideal surgical model at present.